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UCLA study uses genetic profiling to distinguish types of leprosy

New approach may provide new way to diagnose, classify and treat diseases

University of California - Los Angeles

UCLA researchers found a distinction in the gene expression of leprosy that accurately classified two different clinical forms of the disease. This is one of the first studies of its kind where genetic profiling distinguished between disease types, possibly leading to new ways to diagnose and treat all types of diseases.

The new UCLA study, published Sept. 12 in the journal Science, also identified genes belonging to a specific family of cells in the immune system that may provide potent anti-inflammatory or immune suppressant properties. These findings offer more insight into the development of leprosy, as well as new approaches to treat diseases in which the immune system causes tissue damage.

"This study is an important milestone in the new science of using genetic profiling to uncover genes linked to responses that lead to disease progression," said principal investigator Dr. Robert L. Modlin, professor of dermatology and microbiology, immunology and molecular genetics and chief, division of dermatology, David Geffen School of Medicine at UCLA. "The study also provides unanticipated insights into pathogens and targets for therapy."

According to Modlin, the future application of genetic profiling is especially interesting for infectious diseases such as leprosy or even a bioterrorist threat like anthrax.

"With genetic technology, we may be able to quickly distinguish between a common cold and early-stage anthrax, leading to earlier diagnosis and quicker treatment," he noted.

UCLA researchers biopsied 11 leprosy patients' skin lesions, which is one of the first symptoms of the disease. Using sophisticated genetic technology and statistical methods, researchers compared expression patterns for the 12,000 genes found in the skin lesions. Researchers found that gene expressions differed for the two types of leprosy -- tuberculoid leprosy and lepromatous leprosy.

"If we can predict the clinical course of disease, we can intervene earlier," said Modlin. "This is very important for lepromatous leprosy, a more severe form of the disease that can lead to major nerve damage and disfigurement."

Researchers also found that the major difference between the gene expressions of the two types of leprosy occurred in a specific family of cells in the immune system called LIR or leukocyte immunoglobin-like receptors. Researchers found that a particular cell called LIR-7 was expressed five times more in the lepromatous lesions than in the tuberculoid lesions.

Further tests and genetic comparisons between the two lesion groups found that LIR-7 activation may actually suppress the immune system's defenses. This may partly explain why some patients suffer from the more severe form of leprosy because these patients' immune systems may be more compromised.

Researchers then used a tuberculosis bacteria sample to test whether LIR-7 activation would suppress the ability of the immune system to directly combat microbial pathogens. Researchers found that LIR-7 blocked the antimicrobial activity of another cell-surface receptor, called TLR or toll-like receptor. LIR-7 reduced TLR's immune response activity from 60 percent to 20 percent.

"The immune suppression ability of LIR-7 offers us more insight into the development of infectious diseases like leprosy and also may offer future therapies for autoimmune diseases such as psoriasis or rheumatoid arthritis, where the goal is to turn off or suppress the immune system's response," said Modlin.

According to Modlin, the next stage of the genetic research will look at leprosy's various complications, including tissue damage and nerve damage, and try to identify which patients are susceptible to these complications.

Leprosy, one of the world's oldest known diseases, is a chronic infectious disease. In 2003, more than 630,000 new cases of leprosy affected people worldwide, according to the World Health Organization. Leprosy continues to be an ongoing issue in developing countries.

Leprosy is caused by the bacterium "Mycobacterium leprae," and affects the skin, peripheral nerves, upper respiratory tract and eyes, and can lead to severe disfigurement of the hands, face and feet. It is uncertain how leprosy is spread, and current treatment includes a multi-drug regimen.

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The study was funded by the National Institutes of Health and the World Health Organization.

Other researchers include Joshua R. Bieharski, Department of Microbiology, Immunology, and Molecular Genetics and Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles; Huiying Li, Thomas G. Graeber and David Eisenberg, Departments of Chemistry and Biochemistry and Biological Chemistry, Howard Hughes Medical Institute, UCLA -- Department of Energy Institute of Genomics and Proteomics, UCLA, Los Angeles; Christoph Meinken, Martin Rollinghoff and Steffen Stenger, Institut fur Klinische Mikrobiologie, Immunologie, und Hygiene, Universitat Erlangen, Erlangen, Germany; Maria-Teresa Ochoa, Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles; Masahiro Yamamura, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan; Anne Burdick, Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Fla.; Euzenir N. Sarno, Leprosy Laboratory Institute Oswaldo Cruz, Rio de Janeiro, Brazil; Manfred Wagner and Thomas H. Rea, Medizinische Kllnik 3, Kllnikum Nurnberg, Nurnberg, Germany; Marco Colonna, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Mo.; Barry R. Bloom, Office of the Dean, Harvard School of Public Health, Boston, Mass.

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